Childhood-onset unipolar depression impacts school performance, social interactions, and family relationships and is often the beginning of chronic, severe, episodic depression persisting into adolescence and adulthood (Birmaher et al, 2007). Children with unipolar depression are at higher risk for emergent suicidal ideation/behavior, substance abuse, legal problems, physical illness, and early pregnancy (Birmaher et al). Approximately 2 to 4% of children experience either major depressive disorder or dysthymic disorder and 5 to 10% of children and adolescents experience subsyndromal depressive symptoms (Birmaher et al). Due to its prevalence and association with significant current and future functioning deficits, childhood depression warrants treatment research. Treatments include pharmacological and psychotherapeutic interventions, although both have significant limitations in children age 12 and under. A recent meta-analysis found fluoxetine to be the only antidepressant medication with significant empirical support for decreasing depression in children, but concerns about treatment-emergent suicidal ideation/behavior led the Food and Drug Administration to mandate black-box warning for use of antidepressants in this age group (Bridge et al, 2007). Longitudinal data about the developmental impact of antidepressant use are not available. These worries have prompted interest in alternative therapies including dietary supplements, in particular, omega-3 fatty acids (?3). Research on treatment of mood disorders with ?3 is promising (Schacter et al, 2005);however, only one RCT has been conducted in children, which was positive (Nemets et al, 2006). Findings from other clinical populations (ADHD, adolescent depression, anxiety and pervasive developmental disorders in children) suggest combination treatments are advantageous (Aman et al., 2009;The MTA Cooperative Group, 1999a,b, 2004a,b;The TADS Team, 2007;Walkup et al., 2008). However, surprisingly little is known about the effectiveness of psychotherapy for children age 12 and under who are clinically depressed. Randomized controlled trials (RCTs) of cognitive-behavioral therapy (CBT) have been conducted via school- based programs for children with elevated mood symptoms rather than for clinic-referred children diagnosed with a depressive disorder. Several researchers are beginning to develop and test manual-based individual/family therapies for clinic-referred children with diagnosable depression (Kovacs et al, 2006;Tompson et al, 2007);however, no RCTs have been completed. Existing research supports incorporating psychoeducation about depression, support, and skill building to decrease depressive symptoms (Birmaher et al). We previously developed and tested psychoeducational psychotherapy (PEP) for children aged 8-12 with mood disorders. The current study compares ?3, PEP, and their combination to a placebo supplement and active monitoring (AM) in a 12-week trial of 60 children with unipolar depression. Participants may not participate in treatment for depression outside the study from one month prior to participation throughout the 12-week trial. Primary goals are to determine: 1) feasibility of a) recruiting 60 participants in 24 months;b) retaining participants over a 12-week trial;and 2) effect sizes for ?3, PEP, and combination treatment. Secondary goals are to explore response curves over time, mediators and moderators, treatment response across a broad array of outcome variables, adherence to treatment, and side effects. This pilot study of ?3, PEP, and combined treatment will provide evidence about whether a larger trial is feasible and justifiable. PUBLIC HEALTH RELEVANCE: Childhood onset unipolar depression causes immediate problems in functioning and puts children at risk for additional future difficulties (eg, substance abuse, suicidality, legal problems, relapses of depression). Limitations of current pharmacological and psychotherapeutic treatments have led researchers to explore alternatives for more effective and/or safer treatment options;long-chain omega-3 fatty acids (?3) and family- based psychoeducational psychotherapy (PEP) have promising but non-decisive preliminary results. This small randomized, controlled, double-blinded study will examine feasibility of studying the effects of ?3 dietary supplementation, PEP, and combined treatment on reducing depressive symptoms in children diagnosed with major depressive disorder or dysthymic disorder.